title: Interleukin 15 primes natural killer cells to kill via NKG2D and cPLA2 and this pathway is active in psoriatic arthritis.
abstract: NK cells are large granular lymphocytes that form a critical component of the innate immune system, whose functions include the killing of cells expressing stress-induced molecules. It is increasingly accepted that despite being considered prototypical effector cells, NK cells require signals to reach their full cytotoxic potential. We previously showed that IL-15 is capable of arming CD8 effector T cells to kill independently of their TCR via NKG2D in a cPLA2-dependent process. As NK cells also express NKG2D, we wanted to investigate whether this pathway functioned in an analogous manner and if resting NK cells could be primed to the effector phase by IL-15. Furthermore, to establish relevance to human disease we studied a possible role for this pathway in the pathogenesis of psoriatic arthritis, since there are aspects of this disease that suggest a potential effector role for the innate immune system. We found that PsA patients had upregulated IL-15 and MIC in their affected synovial tissues, and that this unique inflammatory environment enabled NK cell activation and killing via NKG2D and cPLA2. Moreover, we were able to reproduce the phenotype of joint NK cells from blood NK cells by incubating them with IL-15. Altogether, these findings suggest a destructive role for NK cells when activated by environmental stress signals during the pathogenesis of PsA and demonstrate that IL-15 is capable of priming resting NK cells in tissues to the effector phase.
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Fangming
authors.initials: F
authors.lastname: Tang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sally
authors.forename: Cezary
authors.initials: C
authors.lastname: Ciszewski
authors.forename: Valerie
authors.initials: V
authors.lastname: Abadie
authors.forename: Shane A
authors.initials: SA
authors.lastname: Curran
authors.forename: Veronika
authors.initials: V
authors.lastname: Groh
authors.forename: Oliver
authors.initials: O
authors.lastname: Fitzgerald
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Winchester
authors.forename: Bana
authors.initials: B
authors.lastname: Jabri
mesh_terms: D015535:Arthritis, Psoriatic / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection
chemical_list: D016207:Cytokines; D019409:Interleukin-15; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034741:RNA, Small Interfering; D054510:Phospholipases A2, Cytosolic